Pain Control and Sedation Case File

Pain Control and Sedation Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 38

A 66-year-old man fell down a flight of stairs. He sustained several  rib fractures and a small right frontal-parietal cerebral contusion. While in the emergency center,   he developed progressive dyspnea, which led to intubation and mechanical ventilation. Shortly after arrival to the ICU, his nurse notifies you that the patient appears anxious and agitated despite having received 8 mg of morphine sulfate intravenously over the past 1 hour. His heart rate is 110 beats/minute, BP is 146/90 mm Hg, respiratory rate is 28 breaths/minute, Glasgow coma score (GCS) is 10T (E4, MS, V1), and O2 saturation is 100%. He appears uncomfortable and is attempting to remove his monitoring leads and urinary catheter.

⯈ What are the appropriate next steps in assessment?

⯈ What are appropriate interventions at this time?

ANSWER TO CASE 38:

Pain Control and Sedation

Summary: A 66-year-old man fell down the stairs and suffered rib fractures and a small right frontal-parietal cerebral contusion. He is intubated secondary to progressive dyspnea. He now appears agitated, uncomfortable, and in danger of self-harm. 

• Appropriate next steps in the assessment: Identify potential reasons for pain and agitation in this patient using validated scales and establish treatment goals. 
• Appropriate interventions at this time: Administer combination of sedative and analgesic medications. An appropriate combination for this patient is propofol for sedation, titrated to Richmond Agitation Sedation Scale (RASS) of 2, and fentanyl for pain control.

ANALYSIS

Objectives

1. 1 . To learn the principles and strategies for pain and anxiety monitoring in the ICU.
2. 2. To learn the various medication treatment strategies available for pain and sedation management in the ICU.
3. 3. To learn management considerations for mechanically ventilated patients.
4. 4. To learn management considerations for patients who are at risk for developing alcohol, benzodiazepines, and opioids withdrawal.

Considerations

This 66-year-old patient is clearly agitated and has progressed to become a danger to himself, as evidenced by his attempt to remove his catheters and lines. To avoid further self-inflicted harm, his agitation and pain must be immediately addressed. Prior to the next step in management however, we must consider the patient's comorbidities, current injuries, and goals of care. The patient has experienced head trauma and subsequently a rapid onset/offset agent that will permit reassessment of his neurological status would be optimal. The ICU team must evaluate how long they anticipate the patient to require mechanical ventilation based on the severity of his respiratory failure. This initial assessment must occur quickly and will guide the ICU care providers toward particular agents and techniques of sedation and pain management.

Approach To:

Pain and Agitation

CLINICAL APPROACH

The ICU care practitioner is responsible for maintaining the patient's comfort while in the ICU. Mechanically ventilated patients in the ICU can exhibit even further stress superimposed on their acute medical problems; examples of these additional stresses include anxiety related to unfamiliar surroundings, and distress with potential and experienced pain. Agitation, anxiety, and pain can bring about many adverse side effects including increased endogenous catecholamine activity, myocardial ischemia, hypercoagulable and hypermetabolic states, sleep deprivation, and delirium possibly resulting in self-injury via removal of life-sustaining devices. Although such adverse effects should be actively avoided, the care providers must be mindful of the potential detrimental effects associated with pharmacological treatment of pain and agitation. A fine balance must be established to maximize the benefits while minimizing the risks of drug accumulation in tissue stores, which may produce prolonged clinical effects and prolongation of ICU stay.

When considering sedation and pain management, the anticipated duration of treatment and mechanical ventilation should be considered. Addressing the target of intervention will help determine the most practical medication strategies. Very often, a combination of opioids and benzodiazepines are used for analgesia and sedation. Alternatively, other agents may be selected depending on the patient's clinical status (Table 3 8-1). The benzodiazepines (midazolam, lorazepam, and diazepam) have been the cornerstone of anxiolytic, amnestic, and sedative therapy for the ICU patient, while opioids have a long history of efficacy and safety for adequate analgesia in the ICU patient.

Pain is common, and the majority of algorithms incorporate testing for pain, with patient self-report being the most accurate means of assessment if the patient is able to communicate. Self-reporting for pain is facilitated using a numerical rating scale (NRS) or visual aid (Figure 3 8-1). A number of other tools for pain observation such as the behavioral pain scale (BPS) (Table 38-2) and critical pain observation tool (CPOT) have been validated. These tools utilize facial expression, body movement, muscle tension, and ventilator synchrony to help assess one's pain. Notably, the validity of these scales declines with the increased depth of sedation.

Sedation scales, the most common being Ramsay Sedation Scale (RSS), Richmond Agitation Sedation Scale (RASS) (Table 38-3), and Sedation Agitation Scale (SAS) (Table 38-4), are used to direct the management of agitation and establish a target level of sedation for medication titration as well as detecting when oversedation is present. The Ramsay score of 2 or 3 is optimal. In the absence of organic or natural causes of obtundation (ie, central nervous system pathology), a Ramsay score of 5 or 6 represents oversedation.

Once a patient is started on a sedative and analgesic medication, the goal should be to minimize the risk of continued infusion of these agents. A focused downward titration of sedative drugs over time can be accomplished with daily interruption 

Figure 38-1.  Analog Pain Scale. (From Hockenberry MJ, Wilson D: Wong's essentials of pediatric nursing, ed 8, St. Louis, 2009, Mosby. Used with permission. Copyright Mosby.)

of sedative infusions (DIS). Mechanically ventilated patients receiving continuous sedation can benefit from daily interruption in the sedation until the patient is awake, as this strategy is associated with decreases in the duration of mechanical ventilation and ICU length of stay. DIS minimizes drug accumulation and shortens the duration of mechanical ventilation. Both sedative and analgesic agents should be interrupted once daily, unless there is evidence for ongoing patient distress. Once drugs are interrupted, the ICU team must be vigilant for evidence of patient distress-overt physical agitation, hemodynamic lability (HTN or tachycardia) , or ventilator asynchrony. A bolus should be given to de-escalate symptoms and restart both sedative and analgesic drugs at half the previous infusion doses with subsequent titration. Performing DIS in every patient may not be appropriate, as there is some concern that DIS could provoke brief episodes of intense withdrawal from drugs or alcohol in those patients at high risk. Further research is needed to clarify the most optimal approach to selecting patients for DIS, though at the discretion of the ICU physician, DIS can be beneficial to the right patient.

Selection of Pharmacologic Therapy

In agitated and anxious patients, the clinician can first attempt nonpharmacologic interventions such as comfortable positioning, verbal reassurance, and encouraging the presence of family and friends, though such interventions are often inadequate alone and ultimately require medical intervention. On initial assessment of

the patient's agitation in the clinical example in this chapter, we can place him at a RASS +3 , since he is removing his catheters and is clearly agitated. Because the patient is awake, we can ask him directly about pain, instructing him to quantify his pain numerically if he is able to do so.

Prior to initiating a sedation and pain regimen in an ICU patient, the patient's injuries, comorbidities, and goals of care must always be addressed. The patient discussed earlier has experienced head trauma for which frequent neurologic examinations may be necessary in the immediate observation period. In this situation, propofol may be the best choice given its rapid onset and offset. Midazolam (Versed) can also be used as a sedative in this patient, although its offset is longer than propofol and frequent neurologic examinations would not be as easy to administer. When initiating a sedative agent, a level of sedation should always be identified-that is, using the RASS sedation scale as a guideline. An appropriate level of sedation would allow the patient to be easily awakened and comfortable, consistent with RASS-1 or -2. Sedation and analgesia in the ICU is multidisciplinary, as the bedside nurses

will be the crucial component of evaluating the patient's sedation level. A s such, it is important to communicate the sedation goals with the entire health-care team.

Opioids are the mainstay of analgesic care in the ICU. These drugs are also very good at palliating coughing and the subjective sense of dyspnea-particularly important for patients who are mechanically ventilated. Among the opioids, fentanyl has a rapid onset of action (1 minute) and rapidly redistributes into peripheral tissues, resulting in a short half-life (0.5-1 hour) after a single dose. As a continuous infusion, fentanyl can be titrated to the patient's comfort as identified by a pain scale as described earlier. If the patient is easily awakened, we can address pain by simply asking the patient to quantify the pain. If the patient is not easily awakened, tools such as facial expression, body movement, and ventilator synchrony can be utilized, again with the bedside nurse being the most important person in this assessment.

After initiation of sedation and analgesia, it is important to continuously reevaluate the clinical status. If the patient appears to be improving from a respiratory standpoint and is prepared to undergo spontaneous breathing trials in preparation for extubation, the patient's sedation should be titrated downward and the patient slowly awoken, as sedation can hinder one's respiratory status. The ICU clinician must be vigilant in this aspect-always reassessing the patient's clinical status and de-escalating medications (or escalating medications if needed) to minimize the risks of medical sedation and analgesia.

Sedation and Analgesic Selection for the Mechanically Ventilated Patients

Patients in need of mechanical ventilation generally require sedation and/or analgesic medication to overcome the stress and discomfort associated with ventilation. As patients who require prolonged ventilatory support progress toward extubation, sedation and analgesic agents are generally decreased. Medication tapering at this time must be done in a way to avoid withdrawal symptoms, avoid over-sedation, and provide adequate comfort so that the patient is able to cooperate with the transitional process.

Agitation Related to Substance Ingestion or Administration

Alcohol abuse contributes to a number of health problems; consequently, it is not uncommon to encounter patients with chronic alcohol ingestion history in the ICU. Chronic excessive alcohol consumption causes depression of the central α- and β-receptors and increase in the inhibitory neurotransmitter GABA. At the same time, chronic alcohol use causes an increase in NMDA receptors, which are responsible for central excitatory activities. When alcohol consumption stops in an individual with a chronic consumption history, the combination of excess excitatory activities and the withdrawal of inhibitory activities can cause symptoms of withdrawal, which include a number of neuropsychiatric and hemodynamic manifestations. Alcohol withdrawal symptoms may include tremulousness (onset within hours, peak 10-30 hours, subsides at approximately 40 hours), seizures (onset 6-48 hours, peak 13-24 hours), hallucination (onset 8-48 hours, may persist 1-6 days), and delirium tremens (onset 48-96 hours). Recognition of patients at risk for alcohol withdrawal is important and can be determined based on social history and history of withdrawal episodes. The treatments are supportive care and benzodiazepines administration, and in some cases of delirium tremens, the addition of propofol and neuroleoptics may be considered.

Chronic ingestion and the administration of exogenous opioids lead to diminished endogenous opioid peptides, therefore when exogenous opioids are abruptly discontinued, the patients may develop withdrawal symptoms. Early symptoms of opioid withdrawal may include yawning, rhinorrhea, sneezing, and seating. Later manifestation of withdrawal may include restlessness, irritability, tachycardia, tremor, hyperthermia, vomiting, and muscle spasm. Withdrawal symptoms may begin within 6 to 12 hours after the last dose of short-acting opioid or after 36 to 48 hours of the last dose of long-acting opioids such as methadone. Withdrawal can occur when long-term administration of opioids is discontinued or tapered too rapidly. A course of tapering over days to weeks may be implemented to avoid this problem.

Benzodiazepine withdrawal can occur in the ICU setting when infusions are decreased or interrupted. Patients receiving higher doses of the medications for prolonged periods of time (> 7 days) have increased susceptibility for developing withdrawal. Close monitoring and slow tapering schedules may be needed when considering benzodiazepine discontinuation in the ICU patients.

CLINICAL CASE CORRELATION

• See also Case 8 (Airway Management/Respiratory Failure), Case 9 (Venti­lator Management), and Case 30 (Altered Mental Status). 

COMPREHENSION QUESTIONS

38.1  A 45-year-old man with multiple abdominal gunshot wounds is intubated in the ICU and has been receiving continuous infusion of propofol and fentanyl for 3 days. His morning labs reveal a potassium count of 6.3 mEq/L, bicarbonate of 16 mEq/L, and the patient had 3 episodes of unsustained ventricular tachycardia overnight. What is your next step in management?

A. Administer calcium gluconate, insulin, and β-blockers for his hyperkalemia.

B. Opt for cardioversion.

C. Discontinue propofol.

D. Resuscitate with fluids to increase bicarbonate.

E. Opt for hemodialysis.

38.2  A 37-year-old woman is admitted to the ICU for severe pancreatitis complicated by acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. She continues to have difficulty ventilating and agitation on increasing doses of fentanyl and midazolam (Versed) IV infusions. What is the most appropriate next step?

A. Continue to increase midazolam (Versed) as tolerated.

B. Change sedative agent from midazolam (Versed) to propofol.

C. Administer a neuromuscular blocking agent in addition to current regimen.

D. Administer a second analgesic as difficulty in ventilating her and agitation are secondary to poorly controlled pain.

E. Provide a trial of pressure support ventilation.

38.3  A 67-year-old woman with end-stage renal disease and coronary artery disease is admitted to the ICU for respiratory failure secondary to pneumonia. Which analgesic agent is most appropriate for this patient?

A. Ketorolac

B. Fentanyl

C. Morphine

D. Meperidine

ANSWERS TO QUESTIONS

38.1  C. Propofol infusion syndrome is a rare but serious and potentially fatal adverse effect, typically seen with infusion rates >83 μg/kg/min for more than 48 hours and carries with it a mortality rate of up to 85%. This syndrome is characterized by dysarrhythmias, heart failure, metabolic acidosis, hyperkalemia, and rhabdomyolysis. High-risk patients include those receiving high doses of the drug, those with history of hypertriglyceridemia, and those concurrently receiving parenteral lipids for nutrition. Treatment consists of immediate cessation of propofol infusion and then correction of hemodynamic and metabolic abnormalities.

38.2  C. Some patients may remain delirious, agitated, and have difficulty maintaining ventilation regardless of whether they are on an effective dose of anxiolytic drugs. If the patient is tracheally intubated, mechanically ventilated, and receiving adequate sedation, using a neuromuscular blockade to paralyze the patient is a good option. In patients with ARDS who are difficult to ventilate and often agitated, neuromuscular blockades may be a reasonable alternative to help improve ventilation and gas exchange.

38.3  B. Fentanyl is metabolized by the liver which creates inactive metabolites that are excreted by the kidneys. Because the metabolites are inactive, fentanyl a good choice for patients with renal insufficiency. Morphine is conjugated by the liver to metabolites that include morphine-6-glucuronide, a potent metabolite. Both morphine and morphine-6-glucuronide are eliminated by the kidney, thus patients with renal dysfunction may suffer from prolonged drug effects. Like morphine, meperidine is renally excreted. A metabolite of meperidine, normeperidine, is a potent CNS stimulant that can potentiate seizures, especially in patients with renal dysfunction. Ketorolac is an NSAID that reversibly inhibits cyclooxygenase- 1 and -2 enzymes and is contraindicated in patients with advanced renal impairment as NSAID use may compromise existing renal function.

References

DevlinJW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiaz­epines, propofol, and opioids. Crit Care Clin. 2009;25:431 -449. 

Murray MJ, Bloomfield EL. Sedation and neuromuscular blockade. In: Gabrielli A, La yon AJ, Yu M, eds. Civetta, Tay lor, and Kirby's Critical Care. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2009:961-971. 

Rajaram SS, ZimmermanJL. Substance abuse and withdrawal: alcohol, cocaine, opioids, and other drugs. In: Gabrielli A, Layon AJ, Yu M, eds. Civetta, Ta ylor, and Kirby's Critical Care. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2009:1015-1027. 

Zapanis A, Leung S. Tolerance and withdrawal issues with sedation. Crit Care Nurs Clin N Am. 2005;17:211-223.

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